tert-Butyl acrylate → 3-(2-Formyl-4-hydroxyphenyl)acrylic acid tert-butyl ester

Temperature

80 °C

To a solution of 2-bromo-5-hydroxybenzaldehyde (200 g, 1.0 mole) in propionitrile (6 L) under N2 was added tri-o-tolyl phosphine (75.4 g, 0.25 mol) and diisopropylethylamine (350 mL, 260 g, 2.0 mol). The solution was degassed and purged with N2 three times. To this solution was added tert-butylacrylate (440 mL, 385 g, 3.0 mol) and palladium acetate trimer (27.8 g, 0.12 mol). The mixture was degassed three times and heated to 80° C. over 30 min. After 30 min, the reaction was cooled to ambient temperature and filtered. The solids were washed with acetonitrile. The filtrate was transferred to a separatory funnel with acetonitrile (4 L total) and was extracted with hexanes (4×5 L). The propionitrile/acetonitrile layer was concentrated by rotary evaporation. The residue was dissolved in toluene (4 L) and washed successively with 1N HCl (1 L), water (1 L), and brine (1 L). The organic layer was dried (Na2SO4), filtered, and concentrated to afford crude product as a wet brown solid (293 g). The crude product was dissolved in CH2Cl2 (600 mL) with stirring. To this solution was added hexanes (1.8 L) over ˜2 h, and the resulting slurry was stirred at ambient temperature for 1 h. The slurry was cooled in an ice water bath and stirred for 1 h. The product was isolated by filtration, washed with hexanes, and dried under vacuum to afford the product as a tan solid (199.5 g, 80.6%).

1. customThe solution was degassed
2. custompurged with N2 three times
3. customThe mixture was degassed three times
4. temperaturethe reaction was cooled to ambient temperature
5. filtrationfiltered
6. washThe solids were washed with acetonitrile
7. customThe filtrate was transferred to a separatory funnel with acetonitrile (4 L total)
8. extractionwas extracted with hexanes (4×5 L)
9. concentrationThe propionitrile/acetonitrile layer was concentrated by rotary evaporation
10. dissolutionThe residue was dissolved in toluene (4 L)
11. washwashed successively with 1N HCl (1 L), water (1 L), and brine (1 L)
12. dry with materialThe organic layer was dried (Na2SO4)
13. filtrationfiltered
14. concentrationconcentrated
15. customto afford crude product as a wet brown solid (293 g)
16. stirringthe resulting slurry was stirred at ambient temperature for 1 h
17. temperatureThe slurry was cooled in an ice water bath
18. stirringstirred for 1 h
19. customThe product was isolated by filtration
20. washwashed with hexanes
21. customdried under vacuum

ORD record

ord-a3df57e48ba443cdb4df91f7c77da4fc

Source dataset

uspto-grants-2007_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07282501B2